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Degradation of Dok Proteins During Phagocytosis of Leishmania by Macrophages.

Alvarez de Celis, Hector; Descoteaux, Albert et Duplay, Pascale . Degradation of Dok Proteins During Phagocytosis of Leishmania by Macrophages. In: 11ième Symposium Annuel de Parasitologie Moléculaire du Québec, 7-8 juin 2011, Université McGill.

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Résumé

Dok proteins are adaptor proteins that share structural similarities characterized by an amino-terminal PH domain, a central PTB domain and a carboxy-terminal domain rich in proline and tyrosine residues. Three members of this family, Dok-1, Dok-2 and Dok-3 are expressed in macrophages. In macrophages, Dok proteins are implicated in the negative regulation of signaling in response to LPS and various cytokines and growth factors. We investigated the role and the fate of Dok proteins during the phagocytosis of Leishmania major promastigotes. We compared NOand TNF-a secretion in response to leishmania infection in results show that Dok proteins positively regulate these responses. By confocal microscopy, we showed that Dok1 is recruited to phagosomes containing latex beads and that Dok remained associated to phagosomes during the maturation process. By contrast, Dok1 is absent from phagosomes containing Leishmania promastigotes. Further biochemical analysis revealed that Dok1 is rapidly degraded upon infection and that this degradation is mediated by the surface metalloprotease gp63. Similarly, Dok2 is a substrate of leishmania gp63. In the absence of gp63, Dok1 is recruited to phagosomes containing L. major promastigotes. These results suggest that Dok proteins may be important regulator of macrophage responses to Leishmania infection.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Présentation par affiche
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 03 mai 2018 15:08
Dernière modification: 03 mai 2018 15:08
URI: https://espace.inrs.ca/id/eprint/7108

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